Lutein, zeaxanthin and mammalian development: Metabolism, functions and implications for health
Introduction
In mammals, including humans, pre- and early post-natal development heavily depends on nutrients provided by the mother through the placenta (pre-birth) and during lactation (after-birth) [[1], [2], [3], [4]]. Carotenoids are examples of such nutrients that can be detected in the maternal circulation and milk [5]. Carotenoids are C40 isoprenoid compounds synthesized by plants, algae, and bacteria. In plants, they support photosynthesis, function as precursors of various hormones, and enable critical functions, such as pollination and seed dispersion, by providing the characteristic yellow, red and orange color to many fruits and flowers [[6], [7], [8]]. Mammals obtain dietary carotenoids predominantly through foods of plant origin. Even though hundreds of carotenoids exist in nature, only about 50 of them are commonly present in the human diet, and only about 10 of these can be detected in significant amounts in the human plasma. Examples include β-carotene, α-carotene, β-cryptoxanthin, lycopene, lutein, zeaxanthin, and β-canthaxanthin [9]. Dietary carotenoids have shown beneficial health effects throughout the life cycle due to their potential antioxidant properties, their ability to serves as precursors of vitamin A and to the emerging signaling functions of their metabolites [[10], [11], [12]]. Of note, evidence for their potential harmful activities also exists [[13], [14], [15], [16]]. The majority of the literature on the biological functions of carotenoids centers on their actions in adult tissues and organs. This review will focus on carotenoid metabolism and functions during pre- and early post-natal development. The most well-known contribution of these compounds to mammalian development is linked to the provitamin A activity of certain carotenoids, specifically β-carotene [17]. The essential nutrient vitamin A indeed supports proper mammalian development by exerting critical transcriptional regulatory activities mediated by its active form retinoic acid [18,19]. The emphasis of this review, however, will be on the role of the non-provitamin A carotenoids lutein and zeaxanthin. These carotenoids, which are not only transferred from mother to fetus through the placenta, but are also abundant in the mother's milk [5], are emerging as important modulators of infant and child visual and cognitive development, as well as critical effectors in the prevention and treatment of morbidity associated with premature births [5]. We will provide a general overview of lutein and zeaxanthin metabolism in mammalian tissue. We will also highlight the major advancements and remaining gaps in knowledge in regards to their metabolism and health effects during pre- and early post-natal development.
Section snippets
Chemical structure, food sources and bioavailability
Based on their chemical structure, carotenoids can be classified as carotenes and xanthophylls. Carotenes (such as β-carotene, α-carotene, lycopene and β-cryptoxanthin) are non-oxycarotenoids that may be linear or possess cyclic hydrocarbons at one or both ends of the molecule. Xanthophylls (such as lutein, zeaxanthin, meso-zeaxanthin, astaxanthin and canthaxanthin) are oxygen-containing carotenoids [20]. Lutein and zeaxanthin are also characterized by the presence of a hydroxyl group at both
Intestinal absorption and transport
In contrast to the intestinal uptake of β-carotene that has been shown to be mediated by the receptor SR-BI [38,39], the details of the molecular mechanisms of lutein and zeaxanthin uptake by the enterocytes are still scarce [40,41]. It is generally assumed that, like other carotenoids, upon intestinal absorption lutein and zeaxanthin are incorporated in chylomicrons, together with other dietary lipids. Chylomicrons are rapidly remodeled by lipoprotein lipase in peripheral tissues and then
Tissue uptake
The specific affinity of these xanthophylls to the HDL may control their post-hepatic tissue distribution via a preferential tissue uptake mediated by the receptor for HDL-lipoproteins and others key players involved in cholesterol and/or lipid transport. In humans, the highest levels of these pigments are reached in the macula of the eye where their concentrations range between 0.1 and 1 mM [27,45,46]. Confirming earlier studies indicating that xanthophylls are preferentially taken up by
Metabolism
Another possible explanation for the selective accumulation of the xanthophylls in the macula of humans and primates is linked to the metabolism of these carotenoids in tissues. In mammals, two enzymes - β-carotene-15,15′-oxygenase (BCO1) and β-carotene-9′,10′-oxygenase (BCO2) - are responsible for mediating the cleavage of carotenoids at specific sites of the polyene chain [53]. These two enzymes have different substrate specificity for various carotenoids, different cellular localization and
Lutein, zeaxanthin and pre-natal development
Evidence that lutein and zeaxanthin may play a role in pre-natal life comes from the presence of these carotenoids in the cord blood. Lutein is the most abundant carotenoid in cord plasma and its concentration was strongly correlated with maternal plasma lutein, suggesting a possible role in the neonatal period [64]. In normal pregnancy, plasma levels of lutein/zeaxanthin are stable during the first trimester of gestation (0.46–0.48 μmol/L), increase steadily until the third semester
Lutein, zeaxanthin and early post-natal development
Human milk is the only source of nutrients for the newborn thus enabling his/her optimal growth and development. Moreover, milk is the only dietary source of lutein and zeaxanthin before solid food is introduced [84]. A 9-country survey conducted on breast milk carotenoid composition among 471 women determined that levels of lutein plus zeaxanthin in milk were ∼0.043 μmol/L, but individual country means varied from a low of ∼0.043 μmol/L in the U.S. to a high of ∼0.077 μmol/L in Japan [85]. In
Summary and conclusions
A wide-range of investigations have explored the health effects of lutein and zeaxanthin in the past decades. The majority of the studies focused on the functions of these xanthophylls on visual, neural, and cognitive health and often attributed their beneficial effects to their antioxidant and anti-inflammatory properties [21,82,102]. A still limited but growing body of evidence has recently supported the role of lutein and zeaxanthin also in mammalian development, specifically in relationship
Acknowledgments
The work form the author's laboratory presented in this review was supported by grants R01HD057493, R01HD057493-02S1 and R01HD083331 from the U.S. National Institute of Health (NIH) and by NRI award #2006-35200-16580 from USDA-CSREES, Bioactive Food Component for Optimal Health (31.0).
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